1-214364943-A-T

Position:

• chr1-214364943-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_005401.5(PTPN14):​c.3272-268T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 151,974 control chromosomes in the GnomAD database, including 50,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.81 (50133 hom., cov: 31)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.793

Genes affected

PTPN14 (HGNC:9647): (protein tyrosine phosphatase non-receptor type 14) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an N-terminal noncatalytic domain similar to that of band 4.1 superfamily cytoskeleton-associated proteins, which suggested the membrane or cytoskeleton localization of this protein. It appears to regulate lymphatic development in mammals, and a loss of function mutation has been found in a kindred with a lymphedema-choanal atresia. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 1-214364943-A-T is Benign according to our data. Variant chr1-214364943-A-T is described in ClinVar as [Benign]. Clinvar id is 1178031.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN14	NM_005401.5	c.3272-268T>A		intron_variant		ENST00000366956.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN14	ENST00000366956.10	c.3272-268T>A		intron_variant		1	NM_005401.5	P1
PTPN14	ENST00000543945.5	c.*2548-268T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122598 AN: 151858 Hom.: 50081 Cov.: 31

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.762

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.807 AC: 122703 AN: 151974 Hom.: 50133 Cov.: 31 AF XY: 0.801 AC XY: 59473 AN XY: 74232

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.764

Alfa AF: 0.812 Hom.: 6245

Bravo AF: 0.801

Asia WGS AF: 0.750 AC: 2607 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3002299; hg19: chr1-214538286;